Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex.

GABAergic interneurons play a critical role in maintaining neural circuit balance, excitation-inhibition regulation, and cognitive function modulation. In tuberous sclerosis complex (TSC), GABAergic neuron dysfunction contributes to disrupted network activity and associated neurological symptoms, assumingly in a cell type-specific manner. This GABAergic centric study focuses on identifying specific interneuron subpopulations within TSC, emphasizing the unique characteristics of medial ganglionic eminence (MGE)- and caudal ganglionic eminence (CGE)-derived interneurons. Using single-nuclei RNA sequencing in TSC patient material, we identify somatostatin-expressing (SST+) interneurons as a unique and immature subpopulation in TSC. The disrupted maturation of SST+ interneurons may undergo an incomplete switch from excitatory to inhibitory GABAergic signaling during development, resulting in reduced inhibitory properties. Notably, this study reveals markers of immaturity specifically in SST+ interneurons, including an abnormal NKCC1/KCC2 ratio, indicating an imbalance in chloride homeostasis crucial for the postsynaptic consequences of GABAergic signaling as well as the downregulation of GABAA receptor subunits, GABRA1, and upregulation of GABRA2. Further exploration of SST+ interneurons revealed altered localization patterns of SST+ interneurons in TSC brain tissue, concentrated in deeper cortical layers, possibly linked to cortical dyslamination. In the epilepsy context, our research underscores the diverse cell type-specific roles of GABAergic interneurons in shaping seizures, advocating for precise therapeutic considerations. Moreover, this study illuminates the potential contribution of SST+ interneurons to TSC pathophysiology, offering insights for targeted therapeutic interventions.

Persistent Conjunctival Chemosis after Lower Lid Blepharoplasty: A Comparison of Different Surgical Techniques.

Background: Conjunctival chemosis, a complication of lower blepharoplasty, can cause persistent discomfort and functional disturbances with worsening in the postoperative period following surgery. Methods: A review of the records of the lower blepharoplasty procedures carried out at the Humanitas Research Hospital, Rozzano, Milan, Italy was performed. Patients were categorized into two groups depending on the procedure performed: (1) transconjunctival blepharoplasty with the removal of the fatty lodges with canthopexy and (2) transcutaneous blepharoplasty with the removal of the fatty lodges with lateral canthoplasty. Each group was further divided into two more groups based on the surgical method used, that is either (a) cold blade and disposable cautery or (b) radiofrequency cut and coagulation and colorado tip (respectively 1a, 1b, 2a and 2b). All patients underwent a postoperative follow-up up to 24 months, which included an evaluation of cosmetic appearance, eyelid scarring and the severity of chemosis. The aim of the study was to investigate which of the surgical procedures causes a lower incidence of persistent type 3 conjunctival chemosis. Results: A total of 1047 patients who underwent lower lid blepharoplasty were included in the study. A total of 512 patients underwent transcutaneous blepharoplasty and 535 underwent the transconjunctival procedure. Among the first group of patients, 266 belong to group 1a and 246 to group 1b. In the second group, 264 were categorized as group 2a and 271 as group 2b. The incidence of type 3 chemosis in the transcutaneous blepharoplasty procedure with lateral canthoplasty was statistically significantly higher than in the transconjunctival approach, considering both the cold blade and the radiofrequency (p = 0.012, 0.010, 0.006, 0.004, respectively). Conclusions: A higher incidence of persistent type 3 conjunctival chemosis is associated with lateral canthus surgery and with the use of radiofrequency.

Membranes and Synaptosomes Used to Investigate Synaptic GABAergic Currents in Epileptic Patients.

Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological phenomena that ultimately lead to generation and recurrence of seizures. Using both a "microtransplantation technique" and synaptosomes preparations from drug-resistant temporal lobe epilepsies (TLEs), we used the technique of two-electrode voltage clamp to record GABA-evoked currents, focusing selectively on the synaptic "fast inhibition" mediated by low-affinity GABAA receptors. Here, we report that the use-dependent GABA current desensitization (i.e., GABA rundown, which is evoked by applying to the cells consecutive pulses of GABA, at high concentration), which is a distinguishing mark of TLE, is mainly dependent on a dysfunction that affects synaptic GABAA receptors. In addition, using the same approaches, we recorded a depolarized GABA reversal potential in synaptosomes samples from the human epileptic subicula of TLE patients. These results, which confirm previous experiments using total membranes, suggest an altered chloride homeostasis in the synaptic area. Finally, the lack of a Zn2+ block of GABA-evoked currents using the synaptosomes supports the enrichment of "synaptic fast inhibitory" GABAA receptors in this preparation. Altogether, our findings suggest a pathophysiological role of low-affinity GABAA receptors at the synapse, especially during the fast and repetitive GABA release underlying recurrent seizures.

Ten-Year Follow-Up of Orbital Volume Augmentation With Calcium Hydroxyapatite Filler in Postenucleation Socket Syndrome.

PURPOSE: To describe the efficacy and persistence of injectable calcium hydroxyapatite (CAHY) to correct orbital volume deficit in postenucleation socket syndrome. METHODS: An observational study was conducted as a clinical review of all patients in the authors' practice who received injectable CAHY placed in the extraconal and intraconal space to increase orbital volume with a 10-year follow up. The amount of CAHY to be injected was defined according to the degree of orbital volume deficit. Patients previously treated with radiotherapy or with a conjunctival fornix insufficient to accommodate the external prosthesis were excluded. All the patients with at least 10 years of follow up were included in the study. RESULTS: Thirty-one postenucleation socket syndrome patients received injectable CAHY for orbital volume augmentation, with a 10-year follow up. The mean amount of preoperative relative enophthalmos measured by Hertel's exophthalmometry was 14.16 ± 2.15. An increase in the mean orbital volume of 3.35 ± 0.91 at 6 months and 2.97 ± 1.35 at 10 years was obtained. The mean follow-up was 219 ± 18 months (range, 184-240). Patients demonstrated clinical and cosmetic improvement that was observed to continue for 10 years. The complications were peribulbar ecchymosis, 2 extrusions of the internal prosthesis, and 2 ptosis. CONCLUSIONS: Injectable CAHY provides safe, simple, repeatable, and cost-effective technique to treat volume deficiency in the enophthalmic orbit in the long term. The volume augmentation obtained with this semipermanent filler demonstrated a lasting effect in the orbit with negligible loss of volume at 10 years.

Genicular artery embolization for knee osteoarthritis: Results of the LipioJoint-1 trial.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: This prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0-100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria. RESULTS: Twenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function. CONCLUSION: GAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months.

Repeat Prostatic Artery Embolization with the Addition of a Liquid Embolic Agent: Short-term Results.

RATIONALE AND OBJECTIVES: The long-term effectiveness of prostatic artery embolization (PAE) can be hampered by the recanalization of the previously embolized prostatic arteries (PA). The use of a liquid embolic agent (LEA) could limit this risk. The purpose of this study was to assess the safety and efficacy of repeat PAE (rePAE) using a LEA (Squid Peri) coupled with microspheres in patients experiencing recurring symptoms after initial embolization. MATERIALS AND METHODS: This retrospective single-center study included all consecutive patients who underwent rePAE using Squid Peri coupled with microspheres. Angiographic patterns of prostatic revascularization were identified. Outcomes were assessed at the 3-month follow-up using the International Prostate Symptom Score (IPSS) and the Quality of Life (QoL) score. The primary endpoint was clinical success defined as an IPSS < 18 with > 25% decrease and a QoL score ≤ 3 with ≥ 1 point decrease. Safety was assessed by using the modified Clavien-Dindo classification. RESULTS: 30 consecutive men (mean age: 67.1 ± 9.5 years) were included. Recanalization of the previously embolized PA was found in 83.3% of patients. Technical success was 93.3%. Median follow-up was 4.9 months [IQR: 3.9 - 9.8]. Clinical success rate was 76.7%, with a mean decrease in IPSS of -9.3 ± 7.3 (p < 0.001) and a median decrease in QoL of -2 [IQR: - 4 - - 1] (p < 0.001). One patient presented with an acute urinary retention requiring readmission (grade IIIa complication). CONCLUSION: Repeat PAE using Squid Peri coupled with microspheres is safe and effective for patients with recurring symptoms after initial embolization.

Exploring a Novel Technique to Tackle the Shortage of Devices for Hepatic Arterial Infusion Chemotherapy: Early Results of an Alternate Approach for Percutaneous Arterial Port Catheter Placement.

Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. We retrospectively included patients who underwent a percutaneous placement of a hepatic intra-arterial port catheter in a single tertiary center from February 2021 to June 2022. We examined the patient baseline characteristics, technical features of the modified procedures, technical success rates, complications and oncological outcomes. Fourteen patients (median age: 60 years; q1 = 54; q3 = 70; range: 53-81 years) underwent 15 modified procedures. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien-Dindo classification. The median liver progression free survival was 6.1 months (q1 = 2.5; q3 = 7.2; range: 1.3-11.6). Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices.

Early versus Late Pars Plana Vitrectomy in Vitreous Hemorrhage: A Systematic Review.

Background: Vitreous hemorrhage (VH) is a common vitreoretinal condition causing impairment of vision due to various etiologies. No consensus exists on the best timing for performing pars plana vitrectomy (PPV) in fundus-obscuring VH. Materials and Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards, we conducted a systematic review of the timing of PPV in VH. We assessed the strength of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for all the included publications, in accordance with the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) recommendations. Results: A total of 1731 articles were identified. Following the removal of duplicates and screening of abstracts, 1203 articles remained. Subsequently, a comprehensive full-text review of 30 articles was conducted. Ultimately, 18 articles met the predefined inclusion criteria. Conclusions: Despite the small number of studies on the timing of treatment for VH, the advantage of early over late PPV seems to be a reasonable approach in selected cases, and it might be considered modern standard care.

PERcutaneous transhepatic CHOLangioscopy using a new single-operator short cholangioscope (PERCHOL): European feasibility study.

OBJECTIVES: A new short device for percutaneous endoscopic cholangioscopy was recently developed. However, feasibility and safety has not yet been evaluated. The aim of this study was to assess clinical success, technical success, and adverse events (AEs). METHODS: This observational multicenter retrospective study included all patients who underwent percutaneous cholangioscopy using a short cholangioscope between 2020 and 2022. The clinical success, defined as the complete duct clearance or obtaining at least one cholangioscopy-guided biopsy, was assessed. The histopathological accuracy, technical success, and the AE rate were also evaluated. RESULTS: Fifty-one patients (60 ± 15 years, 45.1% male) were included. The majority of patients had altered anatomy (n = 40, 78.4%), and biliary stones (n = 34, 66.7%) was the commonest indication. The technique was predominantly wire-guided (n = 44, 86.3%) through a percutaneous sheath (n = 36, 70.6%) following a median interval of 8.5 days from percutaneous drainage. Cholangioscopy-guided electrohydraulic lithotripsy was performed in 29 cases (56.9%), combined with a retrieval basket in eight cases (27.6%). The clinical success was 96.6%, requiring a median of one session (range 1-3). Seventeen patients (33.3%) underwent cholangioscopy-guided biopsies. There were four (7.8%) cholangioscopy-related AEs (cholangitis and peritonitis). Overall, the technical success and AE rates were 100% and 19.6%, respectively, in a median follow-up of 7 months. CONCLUSION: Percutaneous endoscopic cholangioscopy with a new short device is effective and safe, requiring a low number of sessions to achieve duct clearance or accurate histopathological diagnosis.

Recurrence of Basal Cell Carcinoma Treated with Surgical Excision and Histopathological Analysis with Frozen Section Technique with Complete Margin Control (CMC-FS): A 15-Year Experience of a Reference Center.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of eyelid malignancy and it is considered to be dangerous due to its proximity to functionally essential organs. Early diagnosis and complete excision of the primary lesion are crucial to prevent infiltration and metastasis. The study aims to evaluate the extent of recurrence in subjects affected by BCC of the upper third of the face treated with surgical eradication and the frozen section technique with complete margin control (CMC-FS), in comparison with the gold standard Mohs micrographic surgery (MMS). MATERIALS AND METHODS: The study included 111 patients with 111 biopsy-proven eyelid BCCs. On clinical examination, all lesions were removed with 2 mm margins clinically free of neoplasm. Prior to reconstruction, CMC-FS analysis of all surgical margins was performed on each tumor for histopathologic confirmation. Subsequently, all margins were presented for the permanent paraffin sections. RESULTS: There were 69 primary carcinomas and 42 secondary carcinomas among the 111 samples. No recurrence occurred in 109 tumors followed-up for at least 5 years, with a total recurrence rate of 1.8%. The median time between lesion excision and diagnosis of recurrence was 20 months. CONCLUSIONS: at 5-year follow-up, CMC-FS guided excision of BCCs of the eyelids resulted in recurrence rates equivalent to MMS. Intraoperative microscopic control of all margins reduced the recurrence rate of the upper third of the facial BCCs, correlating with easier reconstruction with better esthetic and functional outcome.

Antiplatelets and Anticoagulants in Vitreoretinal Surgery: A Systematic Review.

Background: Antiplatelets and anticoagulants have substantially influenced contemporary vitreoretinal surgical practices. The availability of new oral blood thinners has recently spurred a renewed interest in the clinical approach to vitreoretinal surgical conditions since it may be difficult for the surgeon to collect sufficient evidence-based data to decide whether to discontinue or continue such medications. Materials and Methods: We conducted a systematic review on the use of antiplatelets and/or anticoagulants in the perioperative setting in vitreoretinal surgery and their possible complications, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The level of evidence, according to the Oxford Centre for Evidence-Based Medicine (OCEM) 2011 guidelines, and the quality of evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, were assessed for all included articles. Results: In total, 2310 articles were initially extracted, out of which 1839 articles were obtained after duplicates were removed and their abstracts were screened. A total of 27 articles were included in the full-text review. Finally, a remaining 22 articles fulfilled the inclusion criteria. Conclusions: Even though there is just a small number of studies with solid results, the advantage of using antiplatelets and/or anticoagulants in vitreoretinal surgery seems to outweigh the disadvantages, which are mainly related to postoperative hemorrhagic complications.

Benefits of Repeat Prostatic Artery Embolization on Persistent or Recurrent Lower Urinary Tract Symptoms in Patients with Benign Prostatic Hyperplasia.

OBJECTIVES: To evaluate the benefits of repeat prostatic artery embolization (rePAE) for patients with persistent or recurrent symptoms after initial prostatic artery embolization (PAE). MATERIALS AND METHODS: This is a single-center retrospective study of all patients who underwent a rePAE between December 2014 and November 2020 for persistent or recurrent lower urinary tract symptoms. Symptoms were assessed before and after PAE and rePAE, using the International Prostate Symptom Score and quality of life (QoL) questionnaires. Patient characteristics, anatomical presentations, technical success rates, and complications of both procedures were collected. Clinical failure was defined as one of the following: less than 2 points' decrease in QoL, a QoL score higher than 3, acute urinary retention, and secondary surgery. RESULTS: A total of 21 consecutive patients (mean age: 63.8 ± 8.1; [40-75] years) who underwent rePAE were included. The median follow-up after PAE was 27.7 [18.1-36.9]) months and 8.9 [3.4-10.8] months after rePAE. rePAE was performed at a mean of 19 ± 11.1 [6.9-49.6] months following PAE, and the overall clinical success rate was 33% (7/21). In patients undergoing rePAE because of persistent symptoms, the clinical success rate (18%) was non-significantly lower than that for patients treated for recurrent symptoms (50%) [OR 4.5 (95% CI 0.63-32 P = 0.13)]. The main anatomical revascularization pattern was recanalization of the native prostatic artery (29/45, 66%). CONCLUSION: Patients who experience recurrent symptoms after PAE may benefit more from rePAE than those with persistent symptoms after PAE. Clinical success rates seem to be relatively low in both clinical scenarios.

Embolic Decision Making in Musculoskeletal Embolization.

In his pioneering work, Okuno and colleagues demonstrated the benefit of musculoskeletal (MSK) embolization, using imipenem as an embolic agent, in various diseases such as knee osteoarthritis (KOA), adhesive capsulitis (AC), tennis elbow and other sports injuries. As imipenem is a last-resort, broad spectrum antibiotic, its use is often not feasible depending on countries and their drug regulation. Since then, several other studies have used other material products such as microparticles or liquid embolics. In addition, several products in development or that are used in other indications may prove useful after full clinical evaluation of safety and efficacy. In this article we will develop our recommendations, through an analysis of recent publications on MSK embolization.

Long-term outcomes of prostate artery embolization for acute urinary retention: An analysis of 88 patients.

PURPOSE: The purpose of this study was to assess long-term outcome of prostate artery embolization (PAE) in patients presenting with acute urinary retention related to benign prostatic hyperplasia. MATERIALS AND METHODS: All consecutive patients who underwent PAE for acute urinary retention due to benign prostatic hyperplasia from August 2011 to December 2021 in a single institution were retrospectively included. There were 88 men with a mean age of 72 ± 12 (standard deviation [SD]) years (range: 42-99 years). Patients underwent a first attempt of catheter removal two weeks after PAE. Clinical success was defined as the absence of acute urinary retention recurrence. Correlations between long-term clinical success and patient variables or bilateral PAE were searched for using Spearman correlation test. Catheter-free survival was assessed using Kaplan-Meier analysis. RESULTS: Successful catheter removal in the month following PAE was performed in 72 (72/88; 82%) patients and 16 (16/88; 18%) patients had immediate recurrence. Clinical success persisted for 58 (58/88; 66%) patients at long-term follow-up (mean follow-up: 19.5 months ± 16.5 [SD]; range: 2-74 months). Recurrence occurred at a mean of 16.2 months ± 12.2 (SD) (range: 1.5-43 months) post-PAE. Overall, 21 (21/88; 24%) patients of the cohort underwent prostatic surgery, at a mean of 10.4 months ± 12.2 (SD) (range: 1.2-42.4 months) from initial PAE. No correlations between patients variables or bilateral PAE and long-term clinical success were identified. Kaplan-Meier analysis showed a three-year catheter free probability of 60%. CONCLUSION: PAE is a valuable technique for acute urinary retention related to benign prostatic hyperplasia, with a long-term success rate of 66%. However acute urinary retention relapse affects 15% of patients.

GABAergic Neurotransmission in Human Tissues Is Modulated by Cannabidiol.

Recently, the potential use of phytocannabinoids (pCBs) to treat different pathological conditions has attracted great attention in the scientific community. Among the different pCBs, cannabidiol (CBD) has showed interesting biological properties, making it a promising molecule with a high security profile that has been approved for treatment as an add-on therapy in patients afflicted by severe pharmaco-resistant epilepsy, including Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) and tuberous sclerosis complex (TSC). CBD is pharmacologically considered a "dirty drug", since it has the capacity to bind different targets and to activate several cellular pathways. GABAergic impairment is one of the key processes during the epileptogenesis period able to induce a generalized hyperexcitability of the central nervous system (CNS), leading to epileptic seizures. Here, by using the microtransplantation of human brain membranes approach in Xenopus oocytes and electrophysiological recordings, we confirm the ability of CBD to modulate GABAergic neurotransmission in human cerebral tissues obtained from patients afflicted by different forms of pharmaco-resistant epilepsies, such as DS, TSC, focal cortical dysplasia (FCD) type IIb and temporal lobe epilepsy (TLE). Furthermore, using cDNAs encoding for human GABAA receptor subunits, we found that α1ß2 receptors are still affected by CBD, while classical benzodiazepine lost its efficacy as expected.

Early Developmental Changes of Muscle Acetylcholine Receptors Are Little Influenced by Dystrophin Absence in mdx Mouse.

Dystrophin is a cytoskeletal protein contributing to the organization of the neuromuscular junction. In Duchenne muscular dystrophy, due to dystrophin absence, the distribution of endplate acetylcholine receptors (AChRs) becomes disorganized. It is still debated whether this is due to the absence of dystrophin or to the repeated damage/regeneration cycles typical of dystrophic muscle. We addressed this controversy studying the endplate in the first 3 postnatal weeks, when muscle damage in dystrophic (mdx) mice is minimal. By synaptic and extra-synaptic patch-clamp recordings in acutely dissociated mdx and wt muscle fibers, we recorded unitary events due to openings of AChR-channels containing the γ and ε subunit. We also examined AChR distribution at the endplate by immunofluorescence assays. No differences between wt and mdx fibers were found in the γ/ε switch, nor in the AChR organization at the endplates up to 21 postnatal days. Conversely, we detected a delayed appearance and disappearance of patches with high channel opening frequency in mdx fibers. Our data emphasize that the innervation-dependent γ/ε switch and AChR organization in the endplate are not affected by the absence of dystrophin, while extra-synaptic AChR cluster formation and disassembly could be differentially regulated in mdx mice.

GABAA receptor function is enhanced by Interleukin-10 in human epileptogenic gangliogliomas and its effect is counteracted by Interleukin-1ß.

Gangliogliomas (GGs) are low-grade brain tumours that cause intractable focal epilepsy in children and adults. In GG, as in epileptogenic focal malformations (i.e., tuberous sclerosis complex, TSC), there is evidence of sustained neuroinflammation with involvement of the pro-inflammatory cytokine IL-1ß. On the other hand, anti-inflammatory mediators are less studied but bear relevance for understanding seizure mechanisms. Therefore, we investigated the effect of the key anti-inflammatory cytokine IL-10 on GABAergic neurotransmission in GG. We assessed the IL-10 dependent signaling by transcriptomic analysis, immunohistochemistry and performed voltage-clamp recordings on Xenopus oocytes microtransplanted with cell membranes from brain specimens, to overcome the limited availability of acute GG slices. We report that IL-10-related mRNAs were up-regulated in GG and slightly in TSC. Moreover, we found IL-10 receptors are expressed by neurons and astroglia. Furthermore, GABA currents were potentiated significantly by IL-10 in GG. This effect was time and dose-dependent and inhibited by blockade of IL-10 signaling. Notably, in the same tissue, IL-1ß reduced GABA current amplitude and prevented the IL-10 effect. These results suggest that in epileptogenic tissue, pro-inflammatory mechanisms of hyperexcitability prevail over key anti-inflammatory pathways enhancing GABAergic inhibition. Hence, boosting the effects of specific anti-inflammatory molecules could resolve inflammation and reduce intractable seizures.

Hybrid retroperitoneal necrosectomy using a triple-port approach under endoscopic guidance.

Complex walled-off necrosis with a retroperitoneal component represent a therapeutic challenge. Although mini-invasive approaches have been described, hybrid procedures combining surgical, endoscopic and radiological techniques have slightly been evaluated. A 58 years-old male presented with a 20-cm infected multilocular walled-off necrosis. First, endoscopic-ultrasound guided cystogastrostomy using a lumen-apposing metal stent with further necrosectomy was performed, but the access to distal retroperitoneal collection was average.